Sustained kidney biochemical derangement in treated experimental diabetes: a clue to metabolic memory

Autor(es)

de Oliveira, Antonio Anax F. ; de Oliveira, Tiago F. ; Bobadilla, Larissa L. ; Garcia, Camila C. M. ; Berra, Carolina Maria ; de Souza-Pinto, Nadja C. ; Medeiros, Marisa H. G. ; Di Mascio, Paolo ; Zatz, Roberto ; Loureiro, Ana Paula de M.

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, JAN 12 2017.
• Citações Web of Science: 6

Resumo

The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin- induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-beta expression, reduced PGC-1 alpha expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA. The sustained decrease of uric acid clearance in treated diabetes may support the prolonged kidney biochemical alterations observed after tight glycemic control, and this regulation is likely mediated by the sustained decrease of AMPK activity and the induction of inflammation. This manuscript proposes the first consideration of the possible role of hyperuricemia and the underlying biochemical changes as part of metabolic memory in diabetic nephropathy development after glycemic control. (AU)

• Processo FAPESP: 12/08617-4 - Variáveis no controle glicêmico e patogênese da nefropatia diabética: investigação sobre o fenômeno da memória metabólica
• Beneficiário: Antonio Anáx Falcão de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/11747-0 - Marcadores de dano oxidativo e injúria tubular em modelo de nefropatia diabética experimental
• Beneficiário: Larissa Leticia Bobadilla
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 12/21636-8 - Transformação de células epiteliais bronquiais humanas por benzo[a]pireno: processos metabólicos redox e metilação/desmetilação do DNA
• Beneficiário: Tiago Franco de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado